Differential Effects of the Lateral Hypothalamus Lesion as an Origin of Orexin and Blockade of Orexin-1 Receptor in the Orbitoftontal Cortex and Anterior Cingulate Cortex on Their Neuronal Activity

Several studies revealed that orexins may take part in the regulation of the different forms of affective and cognitive processes during wakefulness. The orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC) as an important part of the prefrontal cortex (PFC) have a crucial role in cognitive processes such as reward and decision-making and has a high density of orexin receptor type 1 (OX1Rs). In the present study, to find out the role of OX1Rs in the OFC neurons firing rate, the OX1Rs were inhibited in this area after a10-min baseline recording. In the second part, the lateral hypothalamus (LH) as the main source of orexinergic neurons was inhibited and its effect on the firing rate and activity pattern of the ACC or OFC neurons were detected by using single-unit recording technique in the rats. Results showed that blockade of OX1Rs in the OFC could excite 8 and inhibit 1 neuron out of 11. Besides, the blockade of OX1Rs in the ACC could excite 6 and inhibit 3 neurons out of 10. Also, LH inactivation excited 5 out of 12 neurons and inhibited 6 neurons in the ACC. It excited 8 and inhibited 6 neurons out of 14 in the OFC. These data suggested that blockade of the OX1Rs excited 72% of the neurons, but LH inactivation had an exciting effect on just 50% of neurons in two main subregions of PFC. It seems that the PFC neurons receive the orexinergic inputs from the LH and indirectly from other sources.

Activation of retinal ganglion cells using a biomimetic artificial retina

Objective. Biomimetic protein-based artificial retinas offer a new paradigm for restoring vision for patients blinded by retinal degeneration. Artificial retinas, comprised of an ion-permeable membrane and alternating layers of bacteriorhodopsin (BR) and a polycation binder, are assembled using layer-by-layer (LBL) electrostatic adsorption. Upon light absorption, the oriented BR layers generate a unidirectional proton gradient. The main objective of this investigation is to demonstrate the ability of the ion-mediated subretinal artificial retina to activate retinal ganglion cells (RGCs) of degenerated retinal tissue. Approach. Ex vivo extracellular recording experiments with P23H line 1 rats are used to measure the response of RGCs following selective stimulation of our artificial retina using a pulsed light source. Single-unit recording is used to evaluate the efficiency and latency of activation, while a multielectrode array (MEA) is used to assess the spatial sensitivity of the artificial retina films. Main results. The activation efficiency of the artificial retina increases with increased incident light intensity and demonstrates an activation latency of ~150 ms. The results suggest that the implant is most efficient with 200 BR layers and can stimulate the retina using light intensities comparable to indoor ambient light. Results from using an MEA show that activation is limited to the targeted receptive field. Significance. The results of this study establish potential effectiveness of using an ion-mediated artificial retina to restore vision for those with degenerative retinal diseases, including retinitis pigmentosa (RP).

Effect of Administration of Lidocaine at Body Temperature on Anesthesia Success in Rodent Model: A Behavior and Electrophysiology Study

Introduction: Success in anesthesia administration relieves the perception of pain during surgery. Lidocaine is the most commonly used local anesthetic agent in clinical medicine. Moreover, anesthetic agents' temperature changes can influence cell membrane permeability. Here, the effectiveness of different temperatures of lidocaine (Lid.) on anesthesia success rate in rats has been investigated in rats. Methods: Wistar male rats were pretreated by fast lidocaine or saline injection into hind paw or intradermal cheek at room (RT) and body (BT) temperatures (22 and 37 °C, respectively), and rat behaviors were evaluated by formalin-induced hind paw pain and orofacial pain tests, respectively. Moreover, using a single-unit recording technique, the spontaneous activity of the marginal nerve was recorded at room temperature in RT-Lid. and BT-Lid. groups. Results: Data analysis revealed that lidocaine had significant anti-nociceptive effects in both the BT-Lid. and RT-Lid. groups compared to their control groups (p < 0.05). Also, the number of spikes in the BT-Lid. and RT-Lid. groups was significantly lower than their baselines (p < 0.05). However, lidocaine at body temperature decreased the total time spent licking the hind paw, the number of lip rubbings, and the number of spikes firing about 10–15% compared to room temperature. Conclusion: In both behavioral and neural levels of the study, our results showed that an increase in the temperature of lidocaine toward body temperature could increase anesthesia success rate compared to administration of lidocaine at room temperature. This finding can be considered in the treatment of patients.

Prolonged morphine exposure during adolescence alters the responses of lateral paragigantocellularis neurons to naloxone in adult morphine dependent rats

Introduction Adolescence is a critical period in brain development, and it is characterized by persistent maturational alterations in the function of central nervous system. In this respect, many studies show the non-medical use of opioid drugs by adolescents. Although this issue has rather widely been addressed during the last decade, cellular mechanisms through which adolescent opioid exposure may induce long-lasting effects are not duly understood. The present study examined the effect of adolescent morphine exposure on neuronal responses of lateral paragigantocellularis nucleus to naloxone in adult morphine-dependent rats. Methods Adolescent male Wistar rats (31 days old) received increasing doses of morphine (from 2.5 to 25 mg/kg, twice daily, s.c.) for 10 days. Control subjects were injected saline with the same protocol. After a drug-free interval (20 days), animals were rendered dependent on morphine during 10 days (10 mg/kg, s.c., twice daily). Then, extracellular single-unit recording was performed to investigate neural response of LPGi to naloxone in adult morphine-dependent rats. Results Results indicated that adolescent morphine treatment increases the number of excitatory responses to naloxone, enhances the baseline activity and alters the pattern of firing in neurons with excitatory responses in adult morphine-dependent rats. Moreover, the intensity of excitatory responses is reduced following the early life drug intake. Conclusion It seems that prolonged opioid exposure during adolescence induces long-lasting neurobiological changes in LPGi responsiveness to future opioid withdrawal challenges.

Quantifying Accelerations and Decelerations in Elite Women Soccer Players during Regular In-Season Training as an Index of Training Load

Accelerations (ACC) and decelerations (DEC) are important and frequent actions in soccer. We aimed to investigate whether ACC and DEC were good indicators of the variation of training loads in elite women soccer players. Changes in the training load were monitored during two different selected weeks (considered a “low week” and a “heavy week”) during the in-season. Twelve elite soccer women playing in the French first division wore a 10-Hz Global Positioning System unit recording total distance, distance within speed ranges, sprint number, ACC, DEC, and a heart rate monitor during six soccer training sessions and rated their perceived exertion (RPE). They answered the Hooper questionnaire (sleep, stress, fatigue, DOMS) to get an insight of their subjective fitness level at the start (Hooper S) and at the end of each week (Hooper E). A countermovement jump (CMJ) was also performed once a week. During the heavy week, the training load was significantly greater than the low week when considering number of ACC >2 m·s−2 (28.2 ± 11.9 vs. 56.1 ± 10.1, p < 0.001) and number of DEC < −2 m·s−2 (31.5 ± 13.4 vs. 60.9 ± 14.4, p < 0.001). The mean heart rate percentage (HR%) (p < 0.05), RPE (p < 0.001), and Hooper E (p < 0.001) were significantly greater during the heavy week. ACC and DEC showed significant correlations with most outcomes: HR%, total distance, distance per min, sprint number, Hooper index of Hooper E, DOMS E, Fatigue E, RPE, and session RPE. We concluded that, for elite women soccer players, quantifying ACC and DEC alongside other indicators seemed to be essential for a more complete training load monitoring. Indeed, it could lead to a better understanding of the reasons why athletes get fatigued and give insight into neuromuscular, rather than only energetic, fatigue.

Time-Dependent Recruitment of Prelimbic Prefrontal Circuits for Retrieval of Fear Memory

The long-lasting nature of fear memories is essential for survival, but the neural circuitry for retrieval of these associations changes with the passage of time. We previously reported a time-dependent shift from prefrontal-amygdalar circuits to prefrontal-thalamic circuits for the retrieval of auditory fear conditioning. However, little is known about the time-dependent changes in the originating site, the prefrontal cortex. Here we monitored the responses of prelimbic (PL) prefrontal neurons to conditioned tones at early (2 h) vs. late (4 days) timepoints following training. Using c-Fos, we find that PL neurons projecting to the amygdala are activated early after learning, but not later, whereas PL neurons projecting to the paraventricular thalamus (PVT) show the opposite pattern. Using unit recording, we find that PL neurons in layer V (the origin of projections to amygdala) showed cue-induced excitation at earlier but not later timepoints, whereas PL neurons in Layer VI (the origin of projections to PVT) showed cue-induced inhibition at later, but not earlier, timepoints, along with an increase in spontaneous firing rate. Thus, soon after conditioning, there are conditioned excitatory responses in PL layer V which influence the amygdala. With the passage of time, however, retrieval of fear memories shifts to inhibitory responses in PL layer VI which influence the midline thalamus.

Resting-state dopaminergic cell firing in the ventral tegmental area negatively regulates affiliative social interactions in a developmental animal model of schizophrenia

Hyperdopaminergic activities are often linked to positive symptoms of schizophrenia, but their neuropathological implications on negative symptoms are rather controversial among reports. Here, we explored the regulatory role of the resting state-neural activity of dopaminergic neurons in the ventral tegmental area (VTA) on social interaction using a developmental rat model for schizophrenia. We prepared the model by administering an ammonitic cytokine, epidermal growth factor (EGF), to rat pups, which later exhibit the deficits of social interaction as monitored with same-gender affiliative sniffing. In vivo single-unit recording and microdialysis revealed that the baseline firing frequency of and dopamine release from VTA dopaminergic neurons were chronically increased in EGF model rats, and their social interaction was concomitantly reduced. Subchronic treatment with risperidone ameliorated both the social interaction deficits and higher frequency of dopaminergic cell firing in this model. Sustained suppression of hyperdopaminergic cell firing in EGF model rats by DREADD chemogenetic intervention restored the event-triggered dopamine release and their social behaviors. These observations suggest that the higher resting-state activity of VTA dopaminergic neurons is responsible for the reduced social interaction of this schizophrenia model.

Anomalous low impedance for small platinum microelectrodes

Electrical measurement of the activity of individual neurons is a primary goal for many invasive neural electrodes. Making these “single unit” measurements requires that we fabricate electrodes small enough so that only a few neurons contribute to the signal, but not so small that the impedance of the electrode creates overwhelming noise or signal attenuation. Thus, neural electrode design often must strike a balance between electrode size and electrode impedance, where the impedance is often assumed to scale linearly with electrode area. Here we test this assumption by measuring the impedance at 1 kHz for differently sized electrodes. Surprisingly, we find that for Pt electrodes (but not Au electrodes) this assumption breaks down for electrodes with diameters of less than 10 microns. For these small sizes, Pt electrodes have impedance values that are up to 3-fold lower than expected. By investigating the impedance spectrum of Pt and Au electrodes we find a transition between planar and spherical diffusion for small electrodes combined with the pseudo-capacitance of proton adsorption at the Pt surface can explain this anomalous low impedance. These results provide important intuition for designing small, single unit recording electrodes. Specifically, for materials that have a pseudo-capacitance or when diffusional capacitance dominates the total impedance, we should expect small electrodes will have lower-than-expected impedance values allowing us to scale these devices down further than previously thought before thermal noise or voltage division limits the ability to acquire high-quality single-unit recordings.

Modulatory Effects of Memantine on Neuronal Response Properties in Rat Barrel Cortex

ntroduction: Memantine as N-Methyl-D-aspartic acid (NMDA) receptor antagonist is used in some neurological disorders. It has been reported that memantine has modulatory effects on the somatosensory information processing in healthy subjects. This study investigated the effect of memantine on electrophysiological properties of barrel cortex neurons in male rats. Methods: Single unit recording was used to evaluate the electrophysiological properties of barrel cortex neurons. The neural responses to the principal whisker (PW), adjacent whisker (AW) and combined displacement of two whiskers [20 ms inter-stimulus intervals (ISIs)] were recorded before and 2 hours after memantine gavage (10 mg/kg). A condition test ratio (CTR) was calculated for assessing inhibitory interactions. Results: Two hours after memantine gavage, neuronal ON and OFF responses to PW deflection were decreased. Also, CTR for both ON and OFF responses was decreased following memantine administration. Conclusions: The current study demonstrated that memantine modified neural response properties in the rat barrel cortex.